2, 7-di-(tertiary aminoalkylene)-2, 7-dihydroanthra-[1:9-5:10]-dipyrazoles



3,235,552 Patented Feb. 15, 1966 United States Patent Ice ethyl)-2,7-dihydroanthra-[119-5:10]-dipyrazole, 2,7 di- [fl-(N-methyl-a-piperodyl)-ethyl] 2,7 dihydroanthra- 1:9-52101-dipyrazole 2 7-di-[5-(N-methy1 iperazino)- DROANTHRA-[l.9-5.10]-DIPYRAZOLES P Siegismund Schiitz and Ernst Schraufstiitter, Wuppertal- P PY ]-2 7:d1hydr0anthra-[1:?-5:10]-d1pyrazole, 2,7 d1- Elberfeld, and Marianne Bock, Wuppertal-Sonnborn, 5 [F'PY P PY dlhydfoanthfa Germany, assignors to Farhenfabriken Bayer Akfiendlpyrazole and 2,7-di-('y-diethylamino-5-oxypropyl)-2,7- gfsellschaft, Leverkusen, Germany, a corporation of dihydroanthra-[1:9-5:l0]dipyrazole.

ermany The novel compounds of the invention are prepared by No Drawing. Filed Feb. 9 1962 Ser. No. 172 074 h Claims p y, application be: 5 y Feb. reaction of an ant radipyrazole of the formula.

3,235,552 2,7-DI-(TERTIARY AMINOALKYLENE)-2,7-DIHY- 10 Claims. (or. 260-246) 11 I More particularly, the present invention relates to pharma- 15 the invention being f the formula; with an alkyl halide of the formula:

R and n is as defined above; or by reaction of an anthraw R N A on 3-n -N B B (IV) OH 32 N-N b A- N-R optionally by an oxy, hydroxy or acetoxy group; each of u 5 a N acid amido, acetamino, or benzylamlno radical; R and R N N-oH 3-n,[D-d- N-R1 from their attachment to the nitrogen atom positioned wherein each of the aforesaid formulae each of A, B, B,

sulfur or oxygen moiety; R is a methyl radical or a and capable of being substituted in a manner similar to A methyl radical, the moiety RR R N is connected to A by or by reaction of an anthrapyrazole of the formula:

NNCH a-n (DCEN)n ministered as such, as Well as in the form of their organic l This invention relates to novel substituted anthradipyrazoles and to process for the preparation thereof.

cologically active, basically substituted anthradipyrazoles 1 B and methods for their production; the novel compounds of an) X on A N NN(CH;)n A- N-R Q H l 1-1 n A wherein X is a halogen atom and each of A, B, B, R, R

dipyrazole selected from the formulae: I

II I I wherein A is a straight or branched chain alkylene radical of from 1 to 4 carbon atoms which may be substituted B and B denotes a hydrogen atom, a halogen atom, or R \3& a nitro, sulfo, carboxy, alkyl, sulfonamido, carboxylic 1 l; B

ll are hydrogen atoms, alkyl radicals, or simultaneously, R2 alkylene radicals joined to each other at a point remote and II I @A i R!-N CD 'CH(3n) N 1 H B E R2/ 1:

more nearly adjacent the pyrazole nucleus, said joining R, R R and n is as defined above, D is an alkylene chain, being effected either directly or by means of a nitrogen, straight or branched, containing from 1 to 3 carbon atoms,

valence connecting the nitrogen atom to the alkylene defined above; with a catalytic reducing agent, such as moiety represented by A, provided that when R is a lithium aluminum hydride, which is, in fact, preferred;

a valence of one of the radicals R and R and n is an integer of from 1 to 2. These compounds, when ad- (VI) I and inorganic salts, are particularly useful in the treatment of amoebic infections (e.g., amoebic dysentery and the like in Warm blooded animals).

Illustrative of the novel compounds of the invention are 2,7-di-(fi-dimethylaminoethyl) 2,7 dihydroanthra- [1 :9-5 10] -dipyrazole, 2,7-di-('y-dimethylaminopropyl)- 2,7-dihydroanthra-[129-5:10]-dipyrazole, 2,7-di-[1,3 biswherein each of B, B, D and n is as described above: (diethy1amino)-propyl-(2)] 2,7-dihydroanthra [1:9- with a hydrogenation catalyst, e.g., lithium aluminum 5:10]-dipyrazole, 2,7-di['y-morpholinopropyl] -2,7 dihyhydride, in the presence, optionally, of a secondary amine; droanthra-[1z9-5:10]-dipyrazole, 2,7-di-(B morpholinoor by reaction of an anthraquinone substituted by a halogen atom at each of the l-C and 5-C carbon positions, and having the formula:

(VII) X 0 II I 0 i ll with a compound of the formula:

Preparation of the compound, 2,7-di-( 3-dimethylaminoethyl)-2,7-dihydroanthra-[1:95: dipyrazole,

12 grams of 2,7-dihydroanthra-[1:9-5z5:10] dipyrazole are dissolved in 70 cubic centimeters of absolute alcohol; 2.4 grams of sodium are then introduced and the suspension is stirred until the sodium is dissolved. 33 grams of ,B-dimethyl-aminoethyl chloride are added dropwise at room temperature, the mixture is heated at boiling for 1 /2 hours (90 minutes) and then evaporated to dryness. The residue is dissolved in dilute acetic acid and the solution is then rendered alkaline and shaken with chloroform. After drying and evaporating the chloroform solution, 2,7-di-(B-dimethylaminoethyl) 2,7 dihydroanthra-[1z9-5:10]-dipyrazole is obtained in a good yield as an oil which crystallizes as in the form of its maleate and can be purified by redissolution from methanol/ether. Orange-yellow crystals are obtained which melt at 211 C.213 C. with decomposition.

C22H26N6+C8H803 (606.6)Calculated: C, H, 5.66; N, 13.87. Found: C, 59.10, 58.95; H, 5.66, 5.81;.N, 13.90.

Example 2 Preparation of the compound, 2,7-di('y-dimethylaminopropyl)-2,7-dihydroanthra-[1:9-5z10] dipyrazole of the formula:

24 grams of 2,7-dihydroanthra-[1:95:10]-dipyrazole are suspended in 150 cc. of absolute alcohol; 4.5 grams of sodium are then introduced therein and dissolved and 22 grams of 'y-dirnethylaminopropyl chloride are added dropwise. The mixture is boiled for 90 minutes and worked up as described in Example 1. The naphthalene 1,5-disulphonate of 2,7-di-('y-dimethylaminopropyl)-2,7- dihydroanthra-[1z9-5:10]-dipyrazole is obtained in a good yield and can be redissolved in aqueous ethanol/ ether. The product compound crystallizes with one mol of Water.

C24H3QNG+CIQHBO6SZ+HZO (708.8 )Calculated: C, 57.61; H, 5.69; N, 11.85; S, 9.04. Found: C, 57.08; H, 6.05; N, 11.99; S, 9.30.

Example 3 (a) Preparation of the compound, 2,7-di-[1,3-bis-(diethylamino) propyl-( 2) ]-2,7-dihydroanthra-[1 :9-5 10]- dipyrazole of the formula:

Into a suspension of 27 grams of 2,7-dihydroanthra- [1:9-5:10]-dipyrazole in 210 cubic centimeters of absolute alcohol, 5.4 grams of sodium are introduced and dissolved. 67.5 grams of 1,3-bis-(diethylamino)-propyl chloride-(2) are subsequently added dropwise and the mixture boiled under reflux for 4 hours. The reaction product is subjected to steam distillation and the residue taken up in chloroform. The chloroform solution is shaken with dilute acetic acid; the acetic acid solution is rendered alkaline and the product extracted with chloroform. After drying and evaporating the chloroform solution, 58 grams of 2,7-di-[1,3-bis-(diethylamino)-propyl- (2)] 2,7 dihydroanthra [1:9-5:10] -dipyrazole are obtained as a viscous oil which crystallizes as naphthalene- 1,5-disulphonate from ethanol/ ether or acetone.

C3 H5 N +2(C1 HgS2O (1177.5)Calculated: N, 9.52; S, 10.88. Found: N, 9.23; S, 10.17.

(b) 2,7 di-[v-morpholino-propyl]-2,7-dihydroanthra- {1:9-5:10]-dipyrazole, of the formula:

C23H34N602+ 2 )Calculated: C, 55.17; H, 5.78; N, 9.65. Found: C, 54.68;,H, 6.08; N, 9.75.

(0) 2,7 di (fi-morpholinoethyl)-2,7-dihydroanthra- [1:9-5:10]-dipyrazole, of the formula:

which forms orange crystals; melting point 181 C.- 184 C.

CgsHggNsOg (458.5)Calculated: C, 68.10; H, 6.60; N, 18.33. Found: C, 68.21; H, 6.89; N, 17.76.

((1) 2,7 di [)3-(N-methyl-a-piperidyl)-ethyl]-2,7-dihydroanthra-[l:9-5:10]-dipyrazole, of the formula:

N-Cl)H-CHn-I TI I CH3 which yields yellow crystals, melting point 201 C.- 202 C.

C H N (512.7)Calculated: N, 21.86. Found: 21.89.

(f) 2,7 di [fi-pyrrolidinopropyl]-2,7-dihydroanthra- [1:95:10]-dipyrazole, of the formula:

NOHOH2II\IN H: This latter compound forms yellow crystals.

C H N (454.6)Calculated: N, 18.48. Found: N, 18.61.

Example 4 Preparation of the compound, 2,7-di-('y-diethylaminofi-oxypropyl) -2,7-dihydroanthra-[ 1 9-5 10] dipyrazole ot the formula:

CHzCHI CH CH;

CHaCHg O I I N-OHr- CHa-N-- CHaCH;

20 grams of 1,5-dichloranthraquinone, cc. of ethanol, 20 g. of triethylamine, 10 cc. of pyridine and 30 grams of 3-diethylamino-Z-oxypropylhydrazine are boiled under reflux for 60 hours after the addition of a pinch of copper chloride. The mixture is then evaporated to dryness, the residue taken up in dilute acetic acid, extracted with chloroform, and the acetic acid solution rendered alkaline. The alkaline solution is shaken with chloroform, the chloroform solution dried and concentrated by evaporation. 2,7-di ('y-diethylamino-fl-oxypropyl)-2,7-dihydroanthra-[1 :9-5: 10] -dipyrazole crystallizes from ethyl acetate and can be recrystallized from acetone. Orange crystals are obtained of MP. 154 C.- 156 C.

C H N -O (490.62)Calculated: N, 17.13; 0, 6.52. Found: N, 16.67; 0, 6.83.

What is claimed is:

1. The compound, 2,7-di-(B-dimethylaminoethyl)-2,7- dihydro anthra- 1 9-5 10] -dipyrazole.

2. The compound, 2,7-di-('y-dimethylaminopropyl)- 2,7-dihydroanthra-[ 1 :9-5 10*] -dipyrazole.

3. The compound, 2,7-di-[1,3 b-is-(diethylamino)-propyl- (2) -2,7-dihydroanthra-[ 1 19-5: 10] -dipyrazole.

4. The compound, 2,7-di-[y-morpholinopropyl]-2,7- dihydroanthra- 1 :9-5 10] -dipyrazole.

5. The compound, 2,7-di-(KS-morpholinoethyl)-2,7-dihydroanthra-[ 1 :9-5 10] -dipyrazole.

6. The compound, 2,7-di-[li-(N-methyl-a-piperidyD- ethyl] -2,7-dihydroanthra- 1 :9-5 10] -dipyrazole.

7. The compound, 2,7-di-[p3-N-methy1piperazino-propyl] -2,7-dihydroanthra- [1 :9-5 10] -dipyrazole.

8. The compound, 2,7-di-[B-pyrrolidinopropyl]-2,7- dihydro-anthra- 1 9-5 10] -dipyrazole.

9. The compound, ZJ-dl-(T-dlfithYlfiHllIlO)-fi-hyd1'OXypropyl-2,7-dihydro anthra- 1 :9-5 10] -dipyrazole.

10. A chemical compound selected from the group consisting of 2,7-di-(fi-dimethylaminoethyl)-2,7 -dihydroanthra- 1 9-5 10] -dipyrazole; 2,7-di- (y-dimethylaminopropyl -2,7-dihydroanthra- [1 :9-5 10] -dipyrazole; 2,7- di-[1,3-bis-(diethylamino)-propyl-(2)] 2,7 dihydroanthra-[ 1 :9-5 10] -dipyrazole; 2,7-di- -morpholinopropyn- 2,7-dihydroanthra- 1 9-5 10] -dipyrazole; 2,7-difi-morpholinoethyl)-2,7-dihydroanthra-[1 :9 5:10] dipyrazole; 2,7-di-[ B-(N-methylx-pipe1idy1)-ethyl] 2,7 dihydroanthra- 1 9-5 10] dipyrazole; 2,7-difi-N-methylpiperazinopropyl]-2,7-dihydroanthra-[1 :9-5 10] -dipyrazole; 2,7-di- [p-pyrrolid-inopropyl]-2,7-dihydroanthra-[1:9 5:10] dipyrazole; and 2,7-di-(v-diethylamino-fi-hydroxypropyl)- 2,7-dihydroanthra-[1z9-5 10] -dipyrazole.

References Cited by the Examiner UNITED STATES PATENTS 3,097,209 7/ 1963 J anssen 260-2475 NICHOLAS S. RIZZO, Primary Examiner.

DUVAL T. MCCUTCHEN, Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,235,552 February 15, 1966 Siegismund Schiitz et a1.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 2, lines 26 to 55, reading for that portion of the formula I read column 5, lines 52 to 61, for that portion of the formula, each cccurrence, reading 0 OH II I read I Signed and sealed this 24th day of January 1967.

(SEAL) Attest:

ERNEST W. SWIDER EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

4. THE COMPOUND, 2,7-DI($-MORPHOLINOPROPYL)-2,7DIHYDROANTHRA-(1:9-5:10)-DIPYRAZOLE.
 10. A CHEMICAL COMPOUND SELECTED FROM THE GROUP CONSISTING OF 2,7-DI-(B-DIMETHYLAMINOETHYL)-2,7 - DIHYDROANTHRA-(1:9-5:10)-DIPYRAZOLE; 2,7-DI-($-DIMETHYLAMINOPROPYL)-2,7-DIHYDROANTHRA-(1:9-5:10)-DIPYRAZOLE; 2,7 DI(1,3-BIS-(DIETHYLAMINO)-PROPYL-(2)) - 2,7 - DIHYDROANTHRA(-1:9-5:10-DIPYRAZOLE; 2,7-DI($-MORPHOLINOPROPYL)2,7-DIHYDROANTHRA-(1:9-5:10)-DIPYRAZOLE;2,7 - DI-(B-MORPHOLINOETHYL)-2,7-DIHYDROANTHRA-(1:9-5:10) - DIPYRAZOLE; 2,7-DI-(B-(N-METHYL-A-PIPERIDYL)-)ETHYL - 2,7 - DIHYDROANTHRA-(1:9-5:10)-DIPYRAZOLE; 2,7-DI(B-N-METHYLPIPERAZINOPROPYL-2,7-DIHYDROANTHRA - (1:9-5:10)-DIPYRAZOLE; 2,7-DI(B-PYRROLIDINOPROPYL)-2,7-DIHYDROANTHRA-(1:9 - 5:10) - DIPYRAZOLE; AND 2,7 - DI-($-DIETHYLAMINO-B-HYDROXYPROPYL)2,7-DIHYDROANTHRA-(1:9-5:10-DIPYRAZOLE. 